Extracapsular Extension in Oropharyngeal Squamous Cell Carcinoma: Only Soft Tissue Metastasis Predicts Disease Recurrence but Does so Independent of HPV Status
DH Carpenter, WL Thorstad, J Zhang, JS Lewis, Jr. Washington University, St. Louis, MO
Background: Nodal metastases in head and neck squamous cell carcinoma (SCC) are common and extracapsular extension (ECE) portends a worse prognosis. However, there are no histologic criteria for ECE, nor have there been studies on ECE specifically in human papilloma virus (HPV)-related SCC. This study quantifies the extent of ECE in oropharyngeal SCC with a clear grading system and a particular focus on HPV-related tumors.
Design: Surgically treated oropharyngeal SCC cases with nodal metastases were identified from the department files. All received post op radiation. ECE was graded as 0 (tumor cells within substance of node only), 1 (tumor filling subcapsular sinus with thickened capsule), 2 (tumor ≤1mm beyond capsule), 3 (tumor >1mm beyond capsule), or 4 (soft tissue metastasis;no residual nodal tissue or architecture). Grade was agreed upon by both study pathologists. In-situ hybridization for high-risk HPV and immunohistochemistry for p16 were performed.
Results: Of the 101 cases, there were 13 grade 0, 25 grade 1, 7 grade 2, 19 grade 3, and 37 grade 4 lymph node metastases. 86 had material for testing; 66.2% were HPV positive and 90.7% p16 positive. ECE grades did not correlate with nodal size(p=0.28) or p16 status(p=0.8). In particular, grade 4 ECE was not associated with nodal size(p=0.24) or p16 status(p=0.5). In follow up, 10 patients(9.8%) had disease recurrence with 1(0.9%) local, 4(3.9%) regional, and 7(6.9%) distant failures. In univariate analysis, survival was no different for ECE grade 0 or 1 (no grade 1 patients recurred) while grade 4 was associated with shorter overall(p=0.001), disease specific(p=0.001) and disease free(p=0.002) survival. Multivariate analysis showed, after adjusting for p16, patients with ECE grade 4 had higher risk of recurrence or death(HR=2.2, 95%CI: 0.9-5.4), but the association did not reach statistical significance(p=0.087). In addition, 6 of the 7 patients who developed distant metastases had grade 4 ECE(p=0.009), and all but one of these was p16 positive.
Conclusions: The impact of ECE is diminished in oropharyngeal SCC relative to the other head and neck sites. 62 patients had ECE ≥2, but only 9 (15%) of these had disease recurrence. However, grade 4 ECE/soft tissue metastasis remains a strong predictor to recurrence, particularly distant metastasis, independent of HPV status.
Category: Head & Neck
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 167, Monday Morning